Traumatic brain injury impairs cardiac function independent of chronic cerebral hypoperfusion.

Abstract

Traumatic brain injury (TBI) is a prevalent neurological condition with long-term consequences that extend beyond the brain. Individuals with a history of TBI are at increased risk for cardiovascular complications, but the mechanisms remain poorly understood. Here, we tested the hypothesis that mild-to-moderate chronic cerebral hypoperfusion, modeled via bilateral carotid artery stenosis (BCAS), exacerbates cardiac dysfunction following TBI. Male and female Swiss Webster mice (8-10 wk old) were randomly assigned to Sham, BCAS, TBI, and BCAS + TBI groups. Cerebral blood flow (CBF) was evaluated at rest and after acetazolamide challenge to evaluate cerebrovascular reserve. Neuroinflammation was assessed in the insular cortex, using ionized calcium-binding adapter molecule 1 (IBA-1) and glial fibrillary acidic protein (GFAP) immunostaining. Cardiac function was evaluated using transthoracic echocardiography, and myocardial morphology was detected by hematoxylin and eosin staining. TBI significantly reduced cardiac function in both sexes, whereas BCAS had no effect by itself. Similar structural changes in cardiomyocytes, such as decreased nuclear density and increased nuclear size, were observed in both TBI and BCAS + TBI mice. BCAS alone robustly elicited gliosis in the insular cortex in the absence of cardiac dysfunction. BCAS + TBI also decreased CBF and cerebrovascular reactivity, along with enhanced glial activation in the insula. These results indicate that TBI-elicited cardiac injury is accompanied by neuroinflammation in central autonomic centers, and preexisting cerebral hypoperfusion does not increase cardiac vulnerability. This study highlights the role of the brain-heart axis as a key driving force in post-TBI morbidity and raises the possibility that cerebrovascular health may serve as a mediator of cardiac outcomes following brain injury.TBI impairs cardiac function and induces glial activation in the insular cortex, a key autonomic region. Although mild-to-moderate chronic cerebral hypoperfusion (BCAS) induces gliosis and reduces cerebrovascular reserve, it does not exacerbate TBI-related cardiac dysfunction. Our findings demonstrate that TBI-driven neuroinflammatory signaling, rather than chronic hypoperfusion, underlies cardiac vulnerability after brain injury, highlighting the brain-heart axis as a key contributor to cardiovascular morbidity.